The development or resistance to anti-cancer drugs is the principal cause of chemotherapy failure in cancer patients. The goal of this study is to increase the response to the anti-cancer agent 5-fluorouracil by overcoming tumor cell resistance with a second anti-cancer agent PALA. This study uses a 3X3 factorial design to assess the joint effects of PALA, leucovorin and fluorouracil on various biochemical endpoints in patients with resectable colorectal cancer. The results will provide a basis for improving therapy.